Extra-Amniotic Prostaglandin Induction of Labour Supplemented with Intravenous Oxytocin Following Fetal Death In Utero S. Kehoe, M. J. M. Mylotte
Clinical Research Unit, Department of Obstetrics and Gynaecology, University College, Galway. Abstract A five year retrospective study (1984-1989) was undertaken on 24 consecutive patients with fetal death to ascertain the efficacy, side effects and complications associated with a combination of extra-amniotic prostaglandin E, and intravenous oxytocin to induce labour. Six patients were primigravidae and eighteen multigravidae with inductions carried out at gestations ranging from 16 to 37 weeks (mean 26 weeks and 3 days). The estimated time from fetal death to induction ranged from I day to 3 weeks (mean 8 days). Induction was successful in all cases with a mean induction to delivery time of 9 hours and 30 minutes. The mean dose of prostaglandin required was 0.914 gins and of oxotocin 12.78 I.U.s. Minor side effects were experienced by 16 % of patients though none were serious. This series confirms the combination of extra-amniotic prostaglandin and intravenous oxytocin as an effective means of inducing labour where fetal death has occurred.
TABLE I Patient Characteristics
Introduction Fetal death in utero generates deep grief and emotional response in the patient and her immediate family. While spontaneous labour commonly follows within a few weeks of fetal death, retention of a dead fetus for longer periods can occur ~, especially at earlier gestation 2. Prolongation of the pregnancy adds little benefit to the patient and is not only inconvenient but also perpetuates the mental distress suffered by the patient 3. Induction will not only shorten this period, but has the added advantage of diminishing the risk to the patient of developing a coagnlopathy,which may occur in association with a retained dead fetus of three or more weeksL Patients and Methods Patients with suspected intrauterine death had the diagnosis conf'uaned by ultrasonographic examination. All patients for induction had blood taken for haemoglobin level, platelets, fibrinogen, F.D.P.'s, and clotting times in order to exclude any coagulopathy. A lumbar epidural block was then inserted in conjunction with a urinary catheter. A solution ofPGE 2 ata concentration of 100 ug/ml was constituted in a 30 ml syringe. Under strict sterile conditions, a prostaglandin primed 16 or 18 Foley catheter was introduced into the cervix with the tip positioned extra-amniotically a minimum of 5 cms superior to the cervical os. The catheter bulb was dilated with saline, 1 ml for each week of pregnancy uterine size to a maximum of 30 mls. A dose of 50 ugs of PGEz was injected during the first hour, and 100 ugs for the second hour and thereafter, using an infusion pump. Simultaneously a solution of 15 units of oxytocin in 1 litre of Dextrose 5% was given commencing with a dose of 10 miUiunits per minute and increased by 10 milliunits per minute half hourly until uterine contractions at 1 in 3 minutes was achieved. Contractions were monitored by an external transducer. A maximum dose of 40 milliunits was permitted. Patients with a previous caesarian section were not permitted in excess of 20 milliunits per minute.
Range
Mean
Age
22-38 years
29.8 years
Gravida
0-8
3
Primigravida
6
Gestation
16-37 weeks
26 weeks+3 days
Time from I.U.D. to induction
1-21 days
8 days
intravenous oxytocyin for induction of labour with fetal death was undertaken. The details concerning the range and mean values of patients' age, previous pregnancies, gestational age, fundal height and the interval between fetal death and induction are given in Table 1. One patient, a para 1, had had a previous lower segment caesarean section delivery. All patients were delivered safely and vaginally on the first induction attempt. Nineteen patients (79%) delivered within 12 hours, four others within 18 hours and one patient did not deliver for 27 hours. In this last ease, the syringe was incorrectly attached to the infusion pump, a fact which went unnoticed for 10 hours. Excluding the latter case, the mean induction to delivery time was 9 hours and 30 minutes (+28 mins S.E.M.) (Table II). Placental delivery was achieved in twenty patients by continuous cord traction. Two patients required manual removal of placenta under epidural analgesia, and a further two patients had examination of the uterus under general anaesthesia, but no products of conception were found in either case. Twenty three ofthepatients had a lumbar epidural and the remaining patients received intramuscular pethidine when required.
Results Retrospective analysis of twenty four consecutive patients (1984-1989) who received extra-amniotic prostaglandins and
The total dose of prostaglandin E2 administered ranged from 0.25 mgs to 1.55 mgs with a mean of 0.914 mgs (+0.069 mgs S.E.M.). The amount of oxytocin required ranged from 278
Vol. 159
Extra-amniotic prostaglandin induction with intravenous oxytocin 279
Nos. 9/10/11/12
TABLE II Time Interval from Induction to Delivery Hours
0-4
4-8
8-12
12-14
14-16
18+
Total
9
9
2
2
1
24
37.4
37.4
8.4
8.4
4.2
100
Patient
Number 1 %
4.2
0.7 I.U.'s to 27 I.U.'s with a mean of 12.78 I.U.'s (+1.58 I.U.'s S.E.M.). Ten patients (42.6%) required less than 10 I.U.'s of oxytocin, with another ten requiring between 10 and 20 I.U.'s, and four (16.8%) needing more than this. Recorded complications occurred in four patients (16.8%) but none was serious or life threatening. One patient suffered nausea and vomiting, while another developed a pyrexia of 37.8°C. Investigation of this patient revealed an E. coli urinary tract infection sensitive to Ampicillin which had already been commenced. The patient's temperature was normal within 24 hours: Two patients suffered post partum haemorrhage, but neither required a blood transfusion. One patiem suffered a dural tap. The average hospital stay was 3~h days. Of the twenty four patients, four remained longer than five days, three for supervision of hypertension and one for social reasons. Thirteen patients (54%) were discharged within 2 days of delivery, with eight (29%) remaining for 3 to 5 days. The main pathological findings indicating the cause of fetal death were most commonly placental insufficiency and lethal congenital abnormalities. Of nineteen recorded weights, the range was 26.5 g - 2460 g with an average of 882.3 g. There were 15 female and 9 male fetuses.
Discussion In 1940 the successful managment of abortion usingoestrogen and oxytocic drugs was published - a concept first reported in 1933 ~,6. This method of induction continued until the 1960s when intra-amniotic injection of hypertonic solutions were utilized, but with associated maternal mortality these became unacceptable7. The 1970s saw the advent of prostaglandins. Their use continues as the preferable method for induction of labour with fetal death in utero and have been used intravenously, intramuscularly, vaginally, extra- and intra-amniotically. The benefits of extra-amniotic prostaglandins are evident from this and other series. The success at first induction attempt (100%) compares favourably with other reported methods, i.e. 96.6% with vaginal prostins s, 80% with intravenous prostaglandins9, and 93.75% with intramuscular PGF21°. Besides this, comparisons of the mean induction to delivery time also compares well at 9 hours 30 minutes for this series against 10 hours 42 minutes, 11 hours 8 minutes and 9 hours 15 minutes for the respective studies mentioned. Minor complications only occurred in this series at a rate of
16.8%. Of interest is the fact that only one patient suffered nausea and vomiting which is one of the main side effects associated with the use ofprostaglandins. One series reported on 33 patients using vaginal prostaglandins with a zero incidence of side effects, though with a disappointing inductiondelivery time, with 21% of patients not delivered after 36 hours n. Of the aforementioned series GIT side effects were reported at 50% for vaginal prostaglandinss, 33% for intravenous prostaglandins 9, and 43.7% with intramuscular prostaglandins ~°. The incidence of 3.8% in this series is a significant improvement. The mean dose of PGE 2needed to induce labour was 0.914 gins which was 1/60 to I/4 of that required with vaginal pessariesSand less than the mean doses needed for intramuscular or intravenous therapy (2 mgs and 1.15 mgs respectively)9,1°. The fact that oxytocin was utilized in all patients in this series was influential. A disadvantage of this method of induction is that the patient is rendered immobile with an intravenous line, and catheters inserted into the uterus and bladder. Other methods permit more mobility. As with any mechanical system, failure or misconnection can lead to delay as occurred in one patient in the series. This series reveals that intrauterine, extra-amniotic prostaglandins combined with intravenous oxytocin is a safe and effective method of inducing labour where fetal death has occurred. A high success rate, a low complication rate and paucity of prostaglandin side effects makes it an attractive approach to induction of labour in cases of fetal death in utero.
Acknowledgement The authors wish to acknowledge the support received from Upjohn Ltd. for this study. References
I. Tricomi, V. and Schuyler,G. H, Fetaldeath in utero.Am. J. Obst. & Gynec. 1957: 74, 1092-1097. 2. Foley, M. E. The natural history of the retained dead foetus. Ir. Med. I. 1981: 74, 237-238. 3. Filshie, G. M. The use of prostaglandin E2 in the management of intrauterine death, missed abortion and hydatidfform mole. J. Obstet. and Gynec. Brit. Com. 1971: 78, 87-90. 4. Jiminez, J. M. and Prichard, J. A. Pathogenesis and treatment of coagulated defects resulting from fetal death. Obstet. Gynecol. 1968: 32, 449-454. 5. Jeffcoate, T. N. A. Missed abortion and missed labour. Lancet 1940: 1, 1045-1048. 6. Robinson, A. L., Datnow, M., Jeffcoate, T. N. A. Induction of abortion and labour by means of oestrin. Br. Med. J. 1953: 1,749-754. 7. Cameron, J. M., Davan, A. D. Association of brain damage and therapeutic abortion induced by amniotic fluid replacement. Br. Med. I. 1966: I, 1010-1013. 8. Sonthem, E. M., Gutknecth, G. D., Mohberg, N. R. and Eddman, D. A. Vaginal prostaglandin E2 in the management of fetalintrauterine death. Br. J. Obstet. Gynaecol. 1978: 85, 437-441. 9. Gordon, H., Pipe, N. G.J. Induction of labour after intrauterine death: comparison between prostaglandin E2 and oxytocin. Obstet. Gynecol. 1974: 45, 44-46. 10. Miranda, J. A., Herruzo, A. J., Montoya, F., Huete, A., Mallol, M. C., DeLaorden, A. F. Induction of dead fetus labour with 15-(S)-methyl prostaglandin F2a. Int. J. GYnecol Obstet. 1988: 26, 209-212. 11. O'Herlihy, C. Labourinduction with low-dose intravaginalprostaglandin E2 following intrauterine death. IJ.M.S. 1986: 155, 51-52.
Clinical Research Unit, Department of Obstetrics and Gynaecology, University College, Galway. Abstract A five year retrospective study (1984-1989) was undertaken on 24 consecutive patients with fetal death to ascertain the efficacy, side effects and complications associated with a combination of extra-amniotic prostaglandin E, and intravenous oxytocin to induce labour. Six patients were primigravidae and eighteen multigravidae with inductions carried out at gestations ranging from 16 to 37 weeks (mean 26 weeks and 3 days). The estimated time from fetal death to induction ranged from I day to 3 weeks (mean 8 days). Induction was successful in all cases with a mean induction to delivery time of 9 hours and 30 minutes. The mean dose of prostaglandin required was 0.914 gins and of oxotocin 12.78 I.U.s. Minor side effects were experienced by 16 % of patients though none were serious. This series confirms the combination of extra-amniotic prostaglandin and intravenous oxytocin as an effective means of inducing labour where fetal death has occurred.
TABLE I Patient Characteristics
Introduction Fetal death in utero generates deep grief and emotional response in the patient and her immediate family. While spontaneous labour commonly follows within a few weeks of fetal death, retention of a dead fetus for longer periods can occur ~, especially at earlier gestation 2. Prolongation of the pregnancy adds little benefit to the patient and is not only inconvenient but also perpetuates the mental distress suffered by the patient 3. Induction will not only shorten this period, but has the added advantage of diminishing the risk to the patient of developing a coagnlopathy,which may occur in association with a retained dead fetus of three or more weeksL Patients and Methods Patients with suspected intrauterine death had the diagnosis conf'uaned by ultrasonographic examination. All patients for induction had blood taken for haemoglobin level, platelets, fibrinogen, F.D.P.'s, and clotting times in order to exclude any coagulopathy. A lumbar epidural block was then inserted in conjunction with a urinary catheter. A solution ofPGE 2 ata concentration of 100 ug/ml was constituted in a 30 ml syringe. Under strict sterile conditions, a prostaglandin primed 16 or 18 Foley catheter was introduced into the cervix with the tip positioned extra-amniotically a minimum of 5 cms superior to the cervical os. The catheter bulb was dilated with saline, 1 ml for each week of pregnancy uterine size to a maximum of 30 mls. A dose of 50 ugs of PGEz was injected during the first hour, and 100 ugs for the second hour and thereafter, using an infusion pump. Simultaneously a solution of 15 units of oxytocin in 1 litre of Dextrose 5% was given commencing with a dose of 10 miUiunits per minute and increased by 10 milliunits per minute half hourly until uterine contractions at 1 in 3 minutes was achieved. Contractions were monitored by an external transducer. A maximum dose of 40 milliunits was permitted. Patients with a previous caesarian section were not permitted in excess of 20 milliunits per minute.
Range
Mean
Age
22-38 years
29.8 years
Gravida
0-8
3
Primigravida
6
Gestation
16-37 weeks
26 weeks+3 days
Time from I.U.D. to induction
1-21 days
8 days
intravenous oxytocyin for induction of labour with fetal death was undertaken. The details concerning the range and mean values of patients' age, previous pregnancies, gestational age, fundal height and the interval between fetal death and induction are given in Table 1. One patient, a para 1, had had a previous lower segment caesarean section delivery. All patients were delivered safely and vaginally on the first induction attempt. Nineteen patients (79%) delivered within 12 hours, four others within 18 hours and one patient did not deliver for 27 hours. In this last ease, the syringe was incorrectly attached to the infusion pump, a fact which went unnoticed for 10 hours. Excluding the latter case, the mean induction to delivery time was 9 hours and 30 minutes (+28 mins S.E.M.) (Table II). Placental delivery was achieved in twenty patients by continuous cord traction. Two patients required manual removal of placenta under epidural analgesia, and a further two patients had examination of the uterus under general anaesthesia, but no products of conception were found in either case. Twenty three ofthepatients had a lumbar epidural and the remaining patients received intramuscular pethidine when required.
Results Retrospective analysis of twenty four consecutive patients (1984-1989) who received extra-amniotic prostaglandins and
The total dose of prostaglandin E2 administered ranged from 0.25 mgs to 1.55 mgs with a mean of 0.914 mgs (+0.069 mgs S.E.M.). The amount of oxytocin required ranged from 278
Vol. 159
Extra-amniotic prostaglandin induction with intravenous oxytocin 279
Nos. 9/10/11/12
TABLE II Time Interval from Induction to Delivery Hours
0-4
4-8
8-12
12-14
14-16
18+
Total
9
9
2
2
1
24
37.4
37.4
8.4
8.4
4.2
100
Patient
Number 1 %
4.2
0.7 I.U.'s to 27 I.U.'s with a mean of 12.78 I.U.'s (+1.58 I.U.'s S.E.M.). Ten patients (42.6%) required less than 10 I.U.'s of oxytocin, with another ten requiring between 10 and 20 I.U.'s, and four (16.8%) needing more than this. Recorded complications occurred in four patients (16.8%) but none was serious or life threatening. One patient suffered nausea and vomiting, while another developed a pyrexia of 37.8°C. Investigation of this patient revealed an E. coli urinary tract infection sensitive to Ampicillin which had already been commenced. The patient's temperature was normal within 24 hours: Two patients suffered post partum haemorrhage, but neither required a blood transfusion. One patiem suffered a dural tap. The average hospital stay was 3~h days. Of the twenty four patients, four remained longer than five days, three for supervision of hypertension and one for social reasons. Thirteen patients (54%) were discharged within 2 days of delivery, with eight (29%) remaining for 3 to 5 days. The main pathological findings indicating the cause of fetal death were most commonly placental insufficiency and lethal congenital abnormalities. Of nineteen recorded weights, the range was 26.5 g - 2460 g with an average of 882.3 g. There were 15 female and 9 male fetuses.
Discussion In 1940 the successful managment of abortion usingoestrogen and oxytocic drugs was published - a concept first reported in 1933 ~,6. This method of induction continued until the 1960s when intra-amniotic injection of hypertonic solutions were utilized, but with associated maternal mortality these became unacceptable7. The 1970s saw the advent of prostaglandins. Their use continues as the preferable method for induction of labour with fetal death in utero and have been used intravenously, intramuscularly, vaginally, extra- and intra-amniotically. The benefits of extra-amniotic prostaglandins are evident from this and other series. The success at first induction attempt (100%) compares favourably with other reported methods, i.e. 96.6% with vaginal prostins s, 80% with intravenous prostaglandins9, and 93.75% with intramuscular PGF21°. Besides this, comparisons of the mean induction to delivery time also compares well at 9 hours 30 minutes for this series against 10 hours 42 minutes, 11 hours 8 minutes and 9 hours 15 minutes for the respective studies mentioned. Minor complications only occurred in this series at a rate of
16.8%. Of interest is the fact that only one patient suffered nausea and vomiting which is one of the main side effects associated with the use ofprostaglandins. One series reported on 33 patients using vaginal prostaglandins with a zero incidence of side effects, though with a disappointing inductiondelivery time, with 21% of patients not delivered after 36 hours n. Of the aforementioned series GIT side effects were reported at 50% for vaginal prostaglandinss, 33% for intravenous prostaglandins 9, and 43.7% with intramuscular prostaglandins ~°. The incidence of 3.8% in this series is a significant improvement. The mean dose of PGE 2needed to induce labour was 0.914 gins which was 1/60 to I/4 of that required with vaginal pessariesSand less than the mean doses needed for intramuscular or intravenous therapy (2 mgs and 1.15 mgs respectively)9,1°. The fact that oxytocin was utilized in all patients in this series was influential. A disadvantage of this method of induction is that the patient is rendered immobile with an intravenous line, and catheters inserted into the uterus and bladder. Other methods permit more mobility. As with any mechanical system, failure or misconnection can lead to delay as occurred in one patient in the series. This series reveals that intrauterine, extra-amniotic prostaglandins combined with intravenous oxytocin is a safe and effective method of inducing labour where fetal death has occurred. A high success rate, a low complication rate and paucity of prostaglandin side effects makes it an attractive approach to induction of labour in cases of fetal death in utero.
Acknowledgement The authors wish to acknowledge the support received from Upjohn Ltd. for this study. References
I. Tricomi, V. and Schuyler,G. H, Fetaldeath in utero.Am. J. Obst. & Gynec. 1957: 74, 1092-1097. 2. Foley, M. E. The natural history of the retained dead foetus. Ir. Med. I. 1981: 74, 237-238. 3. Filshie, G. M. The use of prostaglandin E2 in the management of intrauterine death, missed abortion and hydatidfform mole. J. Obstet. and Gynec. Brit. Com. 1971: 78, 87-90. 4. Jiminez, J. M. and Prichard, J. A. Pathogenesis and treatment of coagulated defects resulting from fetal death. Obstet. Gynecol. 1968: 32, 449-454. 5. Jeffcoate, T. N. A. Missed abortion and missed labour. Lancet 1940: 1, 1045-1048. 6. Robinson, A. L., Datnow, M., Jeffcoate, T. N. A. Induction of abortion and labour by means of oestrin. Br. Med. J. 1953: 1,749-754. 7. Cameron, J. M., Davan, A. D. Association of brain damage and therapeutic abortion induced by amniotic fluid replacement. Br. Med. I. 1966: I, 1010-1013. 8. Sonthem, E. M., Gutknecth, G. D., Mohberg, N. R. and Eddman, D. A. Vaginal prostaglandin E2 in the management of fetalintrauterine death. Br. J. Obstet. Gynaecol. 1978: 85, 437-441. 9. Gordon, H., Pipe, N. G.J. Induction of labour after intrauterine death: comparison between prostaglandin E2 and oxytocin. Obstet. Gynecol. 1974: 45, 44-46. 10. Miranda, J. A., Herruzo, A. J., Montoya, F., Huete, A., Mallol, M. C., DeLaorden, A. F. Induction of dead fetus labour with 15-(S)-methyl prostaglandin F2a. Int. J. GYnecol Obstet. 1988: 26, 209-212. 11. O'Herlihy, C. Labourinduction with low-dose intravaginalprostaglandin E2 following intrauterine death. IJ.M.S. 1986: 155, 51-52.
